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The aim of this study was to develop a semi automatic image processing algorithm (AIPA) based on the simultaneous information provided by X-ray and radioisotopic images to determine the biokinetic models of Tc-99m radiopharmaceuticals from quantification of image radiation activity in murine models. These radioisotopic images were obtained by a CCD (charge couple device) camera coupled to an ultrathin phosphorous screen in a preclinical multimodal imaging system (Xtreme, Bruker). The AIPA consisted of different image processing methods for background, scattering and attenuation correction on the activity quantification. A set of parametric identification algorithms was used to obtain the biokinetic models that characterize the interaction between different tissues and the radiopharmaceuticals considered in the study. The set of biokinetic models corresponded to the Tc-99m biodistribution observed in different ex vivo studies. This fact confirmed the contribution of the semi-automatic image processing technique developed in this study.

The article “Preclinical Biokinetic Modelling of Tc-99m Radiophamaceuticals Obtained from Semi-Automatic Image Processing”, written by Luz G. Cornejo-Aragon, Clara L. Santos-Cuevas, Blanca E. Ocampo-Garcia, Isaac Chairez-Oria, Lorenza Diaz-Nieto, Janice Garcia-Quiroz was originally published Online First without open access. After publication in volume [37], issue [6], page [887–898] the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) [2018] and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made

BACKGROUND Clinical studies in women using technetium-99m (Tc)-Bombesin have shown successful radionuclide imaging of breast tumours overexpressing gastrin-releasing peptide receptors (GRPRs). Recent studies have demonstrated that most breast tumours overexpress folate receptors (FRα). AIM The aim of this work was to synthesize the Lys(α,γ-Folate)-Lys(Tc-EDDA/HYNIC)-Bombesin (1-14) conjugate (Tc-Bombesin-Folate), as well as to assess the in-vitro and in-vivo potential of the radiopharmaceutical to target FRα and GRPR. METHODS LysLys(HYNIC)-Bombesin (1-14) was conjugated to folic acid and the product was purified by size-exclusion high-performance liquid chromatography. Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used for chemical characterization. Tc labelling was performed using ethylenediamine-N,N'-diacetic acid/tricine as coligands. In-vitro binding studies were carried out in T47D breast cancer cells (positive for FRα and GRPR). Biodistribution studies and micro-single-photon emission computed tomography/computed tomography imaging were carried out on athymic mice with T47D-induced tumours. RESULTS High-performance liquid chromatography analyses indicated that the radioconjugate was obtained with high radiochemical purity (96±2.1%). In-vitro and in-vivo results showed significant uptake of the radiopharmaceutical in T47D cells and tumours (5.43% ID/g), which was significantly inhibited by preincubation with cold folic acid or cold Bombesin. CONCLUSION The Tc-Bombesin-folate heterobivalent radiopharmaceutical significantly enhances in-vivo tumour uptake because of the concomitant interaction with FRα and GRPR.

Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of alpha(v)beta(3) integrin, thereby inhibiting angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable multimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of 177Lu-AuNP-RGD in athymic mice bearing alpha(v)beta(3)-integrin-positive C6 gliomas and compare it with that of 177Lu-AuNP or 177Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-microPET/CT), histological characteristics and VEGF gene expression (by real-time polymerase chain reaction) in tumor tissues following treatment with 177Lu-AuNP-RGD, 177Lu-AuNP or 177Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 1177Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 +/- 7.9 Gy). These results correlated with the observed therapeutic response, in which 177Lu-AuNP-RGD significantly (p < 0.05) induced less tumor progression, less tumor metabolic activity, fewer intratumoral vessels and less VEGF gene expression than the other radiopharmaceuticals, a consequence of high tumor retention and a combination of molecular targeting therapy (multimeric RGD system) and radiotherapy (177Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177Lu-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular targeting radiotherapy.